iBT-Net: an incremental broad transformer network for cancer drug response prediction.

In modern precision medicine, it is an important research topic to predict cancer drug response. Due to incomplete chemical structures and complex gene features, however, it is an ongoing work to design efficient data-driven methods for predicting drug response. Moreover, since the clinical data cannot be easily obtained all at once, the data-driven methods may require relearning when new data are available, resulting in increased time consumption and cost. To address these issues, an incremental broad Transformer network (iBT-Net) is proposed for cancer drug response prediction. Different from the gene expression features learning from cancer cell lines, structural features are further extracted from drugs by Transformer. Broad learning system is then designed to integrate the learned gene features and structural features of drugs to predict the response. With the capability of incremental learning, the proposed method can further use new data to improve its prediction performance without retraining totally. Experiments and comparison studies demonstrate the effectiveness and superiority of iBT-Net under different experimental configurations and continuous data learning.

Probing size-dependent defects in zinc oxide using synchrotron techniques: impact on photocatalytic efficiency.

In the present study, synchrotron-based X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS) and X-ray excited optical luminescence (XEOL) have been used to investigate the induced defect states in metal oxide nanomaterials. Specifically, two synthesis approaches have been followed to develop unique nano-sized peanut-shaped (N-ZnO) nanostructures and micron-sized hexagonal rods (M-ZnO). XANES analysis at the Zn K-edge revealed the presence of defect states with a divalent oxidation state of zinc (Zn2+) in a tetrahedral structure. Furthermore, XAS measurements performed at the Zn L3,2-edge and O K-edge confirm higher oxygen-related defects in M-ZnO, while N-ZnO appeared to have a higher concentration of surface defects due to size confinement. Moreover, the in-line XEOL and time dependent-XEOL measurements exposed the radiative excitonic recombination phenomena occurring in the band-tailing region as a function of absorption length, X-ray energy excitation, and time. Based on the chronology developed in the defect state improvement, a possible energy band diagram is proposed to accurately locate the defect states in the two systems. Furthermore, the increased absorption intensity at the Zn L3,2-edge and the O K-edge under the UV lamp suggests delayed recombination of electrons and holes, highlighting their potential use as photo catalysts. The photocatalytic activity degrading the rhodamine B dye established M-ZnO as a superior catalyst with a rapid degradation rate and significant mineralization. Overall, this work provides valuable insights into ZnO defect states and provides a foundation for efficient advanced materials for environmental or other optoelectronic applications.

Evolution of superconductivity in K2-xFe4+ySe5: Spectroscopic studies of X-ray absorption and emission.

This study investigates the evolution of superconductivity in K2-xFe4+ySe5 using temperature-dependent X-ray absorption and resonant inelastic X-ray scattering techniques. Magnetization measurements show that polycrystalline superconducting (SC) K1.9Fe4.2Se5 has a critical temperature (T c) of ∼31 K with a varying superconducting volume fraction, which strongly depends on its synthesis temperature. An increase in Fe-structural/vacancy disorder in SC samples with more Fe atoms occupying vacant 4d sites is found to be closely related to the decrease in the spin magnetic moment of Fe. Moreover, the nearest-neighbor Fe-Se bond length in SC samples exceeds that in the non-SC (NS) sample, K2Fe4Se5, which indicates a weaker hybridization between the Fe 3d and Se 4p states in SC samples. These results clearly demonstrate the correlations among the local electronic and atomic structures and the magnetic properties of K2-xFe4+ySe5 superconductors, providing deeper insight into the electron pairing mechanisms of superconductivity.

[Effects of acid stimulation on saliva flow rate and compositions of human parotid and submandibular glands].

OBJECTIVE: To investigate the effect of acid stimulation on salivary flow rate and compositions of human parotid and submandibular glands, so as to provide basis for comprehensive evaluation of salivary gland function in both health and disease status. METHODS: In the study, 210 healthy participants' whole saliva samples were collected under passive drooling, and their parotid gland and submandibular gland secretions were collected by negative pressure suction. 2% citric acid was dropped on the tip of tongue every 1 min for acid stimulation for a total of 5 times to collect stimulated whole saliva, parotid and submandibular gland saliva. The collected saliva was weighed and saliva flow rate was calculated. The K+, Na+, Cl-, Ca2+, total protein, total phosphorus and α-amylase in saliva samples were detected by biochemical analyzer, and the changing features of flow rate and compositions of different kinds of saliva were compared and analyzed. RESULTS: After acid stimulation, saliva flow rate significantly increased. The increase proportion of parotid gland saliva (10.7 folds) was much higher than that of submandibular gland saliva (2.9 folds). The concentrations of Na+, Cl-, Ca2+, total protein and α-amylase in parotid gland saliva increased significantly (P < 0.05), but there was no significant difference in total phosphorus and K+ (P=0.89, P=0.34). The concentration of Na+ and Ca2+ in saliva of submandibular gland increased significantly(P < 0.05), the concentration of total phosphorus decreased significantly(P < 0.05), and the concentration of Cl- increased, but the difference was not significant(P=0.068). There was no significant difference in total protein, K+ and α-amylase (P=0.85, P=0.07, P=0.95). The compound secretion rate of total phosphorus in saliva of submandibular gland remained unchanged(P=0.066), while the secretion rate of K+, Na+, Cl-, Ca2+, total protein and α-amylase significantly increased(P < 0.01). The compound secretion rate of K+, Na+, Cl-, Ca2+, total protein and total phosphorus and α-amylase in parotid gland saliva increased(P < 0.01). The concentrations of Na+, Cl-, K+, total phosphorus, total protein and α-amylase in parotid were higher than those in submandibular gland (P < 0.01), and the concentration of Ca2+ in submandibular gland saliva was significantly higher than that in parotid (P < 0.001). CONCLUSION: The response of parotid to acid stimulation is stronger, and the secretion of submandibular gland is more stable. Acid stimulation significantly influences the concentrations of electrolytes in saliva, and the composited secretion rate is an evaluation index to reflect both flow rate and composition concentration of saliva. The parotid gland plays an important role in the secretion of total protein, total phosphorus and α-amylase in saliva, and the submandibular gland is the main source of Ca2+ in saliva.

The relationship between famine exposure in early life and left atrial enlargement in adulthood.

BACKGROUND: Increased left atrium diameter (LAD) is associated with an elevated risk of cardiovascular diseases. The relationship between nutrition status and left atrial enlargement (LAE) is still unclear. The present study aimed to investigate the association of famine exposure in early life with LAE in adulthood. METHODS: Participants were divided into non-exposed, fetal, early, middle and late childhood exposed groups according to birth data. LAE was defined when LAD was ≥3.9 cm in women and ≥4.1 cm in men, or ≥2.3 cm m-2 by a sex-independent cut-off normalised for body surface area. Multivariate logistic regression was performed to calculate the odds ratio (OR) and confidence interval (CI) between famine exposure and LAE. RESULTS: In total, 2522 [905 male, mean (SD) age 59.1 (3.65) years] subjects were enrolled, including 392 (15.5%) LAE subjects. The prevalence of LAE in non-exposed, fetal, early, middle and late childhood exposed groups was 55 (10.8%), 38 (11.2%), 88 (18.1%), 102 (16.7%) and 109 (19.0%), respectively. Compared to the non-exposed group, the ORs for LAE were in fetal (OR = 0.956, 95% CI = 0.605-1.500, P = 0.847), late (OR = 1.748, 95% CI = 1.208-2.555, P = 0.003), middle (OR = 1.647, 95% CI = 1.140-2.403, P = 0.008) and early (OR = 1.630, 95% CI = 1.116-2.399, P = 0.012) childhood exposed groups after adjusting potential cofounders. When stratified by gender, smoking, body mass index, hypertension and diabetes, we found that the effect of famine exposure on LAE was only modified by diabetes (Pinteraction  = 0.007). CONCLUSIONS: Famine exposure during childhood stage might increase the risk of LAE in adults, and this effect interacts with diabetes.

Hybrid Transfer Learning and Broad Learning System for Wearing Mask Detection in the COVID-19 Era.

In the era of Corona Virus Disease 2019 (COVID-19), wearing a mask can effectively protect people from infection risk and largely decrease the spread in public places, such as hospitals and airports. This brings a demand for the monitoring instruments that are required to detect people who are wearing masks. However, this is not the objective of existing face detection algorithms. In this article, we propose a two-stage approach to detect wearing masks using hybrid machine learning techniques. The first stage is designed to detect candidate wearing mask regions as many as possible, which is based on the transfer model of Faster_RCNN and InceptionV2 structure, while the second stage is designed to verify the real facial masks using a broad learning system. It is implemented by training a two-class model. Moreover, this article proposes a data set for wearing mask detection (WMD) that includes 7804 realistic images. The data set has 26403 wearing masks and covers multiple scenes, which is available at "https://github.com/BingshuCV/WMD." Experiments conducted on the data set demonstrate that the proposed approach achieves an overall accuracy of 97.32% for simple scene and an overall accuracy of 91.13% for the complex scene, outperforming the compared methods.

[Three-dimensional MRI reconstruction research on the anatomical relationship among uterosacral ligament and ureter or rectum in pelvic organ prolapse patients].

Objective: To study the anatomical relationship among uterosacral ligament and ureter or rectum by using MRI three-dimensional reconstruction model in pelvic organ prolapse (POP) patients. Methods: According to the research standard, 67 POP patients were enrolled, who accepted pelvic MRI before surgery in Nanfang Hospital, Southern Medical University during May 2015 to March 2020. Three-dimensional model of uterosacral ligament was reconstructed. The intersection point of the fitting curve of uterosacral ligament and ischial spine level marked point P0, every 1 cm increasing from P0 towards the sacrum marked points P1, P2, and P3. Distances were measured between rectum or ureter to uterosacral ligament respectively at the P0-P3 horizontal levels. Results: (1) The distances between the left ureter and the left uterosacral ligament were (15.45±7.46) to (19.31±11.38) mm, and the distances between the right ureter and the right uterosacral ligament were (13.77±8.16) to (14.78±9.18) mm. At the P1 horizontal level ureters were the closest to uterosacral ligaments, and the right ureter was the closest to right uterosacral ligament [(13.45±9.34) mm] at P2 horizontal level in severe POP group. The farthest distance presented at the P3 horizontal level between bilateral ureters and uterosacral ligaments. (2) At the P0 horizontal level, the rectum was the closest to the bilateral uterosacral ligaments [left: (20.62±9.99) mm, right: (16.82±9.63) mm; P=0.026], and the rectum was closer to the right uterosacral ligament. There were no significant differences in the distance between rectum and bilateral uterosacral ligaments in mild POP group (P>0.05), and the results of severe POP group also showed the rectum was closer to the right uterosacral ligament [(15.64±10.31) mm at P0 horizontal level]. Conclusions: Right ureter and rectum are closer to the right uterosacral ligament. Gynecologists should pay more attention to avoid damaging the right ureter and rectum during the operation of the right uterosacral ligament in POP patients.

Impact of denosumab on cardiovascular calcification in patients with secondary hyperparathyroidism undergoing dialysis: a pilot study.

The receptor activator of nuclear factor-kappa B ligand (RANKL)/RANK/osteoprotegerin system is dysregulated in hyperparathyroid bone diseases. The introduction of denosumab preceding elective surgery as an alternative option when surgery is not possible immediately. INTRODUCTION: The effects of denosumab on vascular calcification in patients with chronic renal failure and low bone mass have been a subject of interest. Therefore, this investigation aimed to determine the short-term changes in vascular calcification after denosumab treatment using a serial electrocardiography-gated computed tomography (CT) to measure coronary artery calcification (CAC) in patients with secondary hyperparathyroidism (SHPT) and low bone mass. METHODS: This 6-month study enrolled patients with SHPT and low bone mass (T-score < - 2.5) owing to dialysis. The 2 groups administered denosumab at a dose of 60 mg (denosumab group), and conventional treatment (control group) had 21 patients each. All patients underwent CT scans at baseline and at the follow-up examination at 6 months to determine the bone mineral density and CAC. RESULTS: The control group demonstrated a significant increase in Agatston scores (187.79 ± 72.27) (P = 0.004). However, no significant change was noted in the denosumab group (P = 0.41). In the denosumab group, only the baseline serum alkaline phosphatase levels correlated negatively with changes in the CAC score (P = 0.01); the baseline alkaline phosphatase levels were the deciding biomarkers for non-responsive CAC scores by Berry Criteria after denosumab treatment (P = 0.02). The denosumab group demonstrated significantly increased bone mineral density in the femoral neck and lumbar spine (P < 0.01). CONCLUSION: The findings provide evidence that denosumab may suppress the progression of CAC and also regress osseous calcification in severe cases of high bone turnover.

Local Water-Filling Algorithm for Shadow Detection and Removal of Document Images.

Shadow detection and removal is an important task for digitized document applications. It is hard for many methods to distinguish shadow from printed text due to the high darkness similarity. In this paper, we propose a local water-filling method to remove shadows by mapping a document image into a structure of topographic surface. Firstly, we design a local water-filling approach including a flooding and effusing process to estimate the shading map, which can be used to detect umbra and penumbra. Then, the umbra is enhanced using Retinex Theory. For penumbra, we propose a binarized water-filling strategy to correct illumination distortions. Moreover, we build up a dataset called optical shadow removal (OSR dataset), which includes hundreds of shadow images. Experiments performed on OSR dataset show that our method achieves an average ErrorRatio of 0.685 with a computation time of 0.265 s to process an image size of 960×544 pixels on a desktop. The proposed method can remove the shading artifacts and outperform some state-of-the-art methods, especially for the removal of shadow boundaries.

[Long-term oncological outcomes of laparoscopic versus abdominal surgery in stage â a1 （LVSI+）-â b1 cervical cancer patients with different tumor size: a big database in China].

Objective: To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI+）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods: Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results: (1) A total of 4 891 patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.367, 95%CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS (HR=1.420, 95%CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS (P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups (P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS (HR=1.705, 95%CI: 1.088-2.674, P=0.020). Conclusions: For patients with stage Ⅰa1 （LVSI+）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Severe hypophosphatemia induced by denosumab in a patient with osteomalacia and tenofovir disoproxil fumarate-related acquired Fanconi syndrome.

Denosumab, a novel agent that inhibits osteoclasts, reduces the risk of fracture in patients with osteoporosis. However, worsening of hypophosphatemia and other symptoms may be induced by denosumab in patients with pre-existing hypophosphatemic osteomalacia. A 58-year-old man with hepatitis B presented with diffuse bone pain and muscle weakness. Denosumab was prescribed by the orthopedist according to documented low bone mass and spine compression fracture. After administering denosumab, the patient's bone pain worsened, and he later developed a right tibia stress fracture. His condition was diagnosed as adult-onset hypophosphatemic osteomalacia complicated by multiple bone fractures, which resulted from Fanconi syndrome with proximal tubulopathy due to tenofovir disoproxil fumarate (TDF) treatment for his hepatitis B. Denosumab use leads to aggressive hypophosphatemic osteomalacia and the complication of stress fractures, because of its effects on bone resorption. Physicians should be aware that in patients with chronic hepatitis B monoinfection who are administered TDF therapy, bone pain or fracture is possible but preventable by timely monitoring of serum phosphate levels. Denosumab should not be used in patients with untreated osteomalacia or vitamin D deficiency, as it may lead not only to hypocalcemia but also to hypophosphatemia in these patients.

Comparison of primary arthrodesis versus open reduction with internal fixation for Lisfranc injuries: Systematic review and meta-analysis.

Objective: Multiple studies have compared primary arthrodesis versus open reduction with internal fixation (ORIF) for surgical treatment of fractures of the Lisfranc joint, but their results have been inconsistent. Therefore, the present systematic review and meta-analysis was performed to compare the clinical efficacy of arthrodesis versus ORIF for the treatment of Lisfranc injuries. Methods: Through searching the Embase, PubMed, PMC, CINAHL, PQDT, and Cochrane Library databases (from July 1998 to July 2018), we identified five case-controlled trials and two randomized controlled trials that compared the clinical efficacy of primary arthrodesis and ORIF for treating Lisfranc injuries. The extracted data were analyzed using Review manager 5.3 software. Results: Through comparisons of data for primary arthrodesis and ORIF groups, we found no significant differences in the anatomic reduction rate, revision surgery rate, and total rate of complications between the different treatment approaches. However, arthrodesis was associated with a significantly better American Orthopedic Foot and Ankle Society (AOFAS) score, return to duty rate, and visual analog scale score with a lower incidence of hardware removal compared with ORIF. Conclusions: For the treatment for Lisfranc injuries, primary arthrodesis was superior to ORIF based on a higher AOFAS score, better return to duty rate, lower postoperative pain, and lower requirement for internal fixation removal. Further evidence from future randomized controlled trials with higher quality and larger sample sizes is needed to confirm these findings.

Cepharanthine, a bisbenzylisoquinoline alkaloid, inhibits lipopolysaccharide-induced microglial activation.

Activation of microglial cells in the brain has been considered to be associated with various neurodegenerative diseases (NDD). In this study, cepharanthine, a bisbenzylisoquinoline alkaloid, was found to inhibit lipopolysaccharide (LPS)-induced microglial activation. Cepharanthine suppressed the release of nitric oxide (NO) by LPS-activated primary mouse cortical microglia and/or BV2 microglial cell line. Cepharanthine reduced LPS-induced mRNA expression of inducible NO synthase (iNOS), but it did not display direct NO-scavenging activity up to 100 µM in sodium nitroprusside (SNP) solution. Further studies revealed that cepharanthine suppressed the release of cytokines (TNF-α, IL-1ß, and IL-6) by LPS-activated microglial cells. Cepharanthine may have potential in the treatment of neurodegenerative diseases accompanied by microglial activation.

[Trend in proportion and clinicopathological characteristics of young women with stage â a2 to â ¡a2 cervical cancer].

Objective: To analyze the 13 years trend in proportion, risks factors and clinicopathological characteristics of young women with stage Ⅰa2 to Ⅱa2 cervical cancer by using multi-center data of cervical cancer in China. Methods: The clinicopathological data of 46 313 patients with cervical cancer treated from 37 hospitals in China were obtained from January 2004 to December 2016. Using clinical and pathologic data, each patient's stage was reclassified by the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system. A total of 19 041 patients were selected according to the following criteria: FIGO stage Ⅰa2 to Ⅱa2, underwent type B or C radical hysterectomy and pelvic lymphadenectomy. All the patients were divided into two groups: the study group of 1 888 patients aged 35 years or younger and the control group of 17 153 patients aged over 35 years. The 13 years trend in proportion of young women with stage Ⅰa2 to Ⅱa2 cervical cancer, risks factors and clinicopathological characteristics of two groups were retrospectively analyzed. Results: (1) The total number of hospitalized patients with stage Ⅰa2 to Ⅱa2 cervical cancer increased annually. However, a downward trend of patients aged 35 years or younger was observed (P<0.01) . The constituent ratio of patients aged 35 years or younger was significantly greater during 2004-2010 than that during 2011-2016 [12.6% (820/6 484) and 8.5% (1 068/12 557) , respectively; χ(2)=82.101, P<0.01]. (2) Compared with patients aged over 35 years, patients aged 35 years or younger had an earlier age at menarche, a later age at marriage, lesser gravida and parity (all P<0.01). The positive rate of high-risk HPV infection was not statistically different between two groups (all P>0.05). (3) The proportions of stage Ⅰ, exophytic type and non-squamous histological type in patients aged 35 years or younger were clearly higher than those in patients aged over 35 years (83.4% vs 68.5%, P<0.01; 63.2% vs 56.2%, P<0.01; 13.9% vs 12.0%, P<0.05, respectively). Whereas the poor differentiation ratios of the two groups had no statistical significance (P>0.05). (4) As for the postoperative pathological risk factors, the rate of surgical margin involvement in patients aged 35 years or younger was lower than that aged over 35 years (1.1% vs 1.8%, P<0.05), and the rate of depth of stromal invasion >1/2 in patients aged 35 years or younger was lower than that in patients aged over 35 years (40.1% vs 50.9%, P<0.01). In addition, there were no significant difference in parametrial margin involvement, tumor size and lymph vascular space invasion between two groups (all P>0.05). Conclusions: The trend in proportion among hospitalized patients for stage Ⅰa2 to Ⅱa2 cervical cancer in young women is decreasing yearly. Compared with cervical cancer in middle-aged and elderly women, cervical cancer in young women have an earlier age at menarche, a higher proportion of stage Ⅰ patients and non-squamous histological type. In terms of the postoperative pathological risk factors, the rate of surgical margin involvement and depth of stromal invasion >1/2 in young women with cervical cancer are lower than in middle-aged and elderly women.

AFP role in predicting recurrence of hepatocellular carcinoma after living donor liver transplantation in HCV patients.

HCC is one of the leading causes of death worldwide. Liver transplantation including living donor transplantation is the best available treatment. We have analyzed our experience with LDLT in patients with HCC and HCV in order to determine if alpha feto-protein (AFP) is a better predictor of recurrence than the tumor burden. We have identified all patients with HCV related liver disease and HCC who have undergone LDLT in one center during the period from December 2000 to December 2014. Outcomes from the prospective database were compared for patients who met Milan criteria (single tumor ≤5 cm, maximum of 3 total tumors with none >3 cm) or not. Uni- and multi-variable analyses of factors influencing recurrence free survival (RFS) were performed. A total of 142 patients with HCC and HCV associated liver disease underwent LDTL during the study period. RFS was 96.4% at 1 years, 91.8% at 3 years and 91.8% at 5 years. Gender, model for End-Stage Liver disease (MELD), pre-transplant therapy, AFP level, tumor number, total tumor size were predictors of recurrence on univariable analysis. On multivariable analysis MELD score (Hazard ratio (HR) 1.16) and Log10 AFP (HR 3.14) were predictors of RFS. In the ROC curve analysis with an AUC of 0.76 the optimal cut-off value of AFP was 26ng/mL. In conclusion MELD score and pre-transplant AFP predict recurrence after LDLT for HCC with HCV infection.

Altered oesophageal mechanosensitivity of secondary peristalsis as a pathophysiological marker in patients with globus sensation.

OBJECTIVE: Secondary peristalsis is important for clearance of retained food bolus and refluxate from the oesophagus. We aimed to investigate whether patients with globus sensation have altered physiological characteristics of secondary peristalsis. DESIGN: Prospective case-controlled study SETTING: Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. PARTICIPANTS: Seventeen globus patients and 18 healthy controls. MAIN OUTCOME MEASURES: After a baseline recording of primary peristalsis, secondary peristalsis was stimulated with slow and rapid mid-oesophageal injections of air. Distension thresholds and peristaltic activities of secondary peristalsis were analysed and compared between the patients and healthy controls. RESULTS: The threshold volume for generating secondary peristalsis during slow air distension did not differ between the patient and control groups (P = .55). The threshold volume for generating secondary peristalsis during rapid air distension was significantly greater in patients with globus than healthy controls (7.0 ± 0.9 vs 5.0 ± 0.3 mL, P = .04). Secondary peristalsis was triggered less frequently in globus patients as compared with healthy control after rapid air distension (40% [30%-65%] vs 60% [60%-83%], P = .001). There was no difference in any of peristaltic parameters for primary and secondary peristalsis between the groups. CONCLUSIONS: Our work identifies functional defects of oesophageal secondary peristalsis in patients with globus sensation and such defects are characterised with defective triggering of secondary peristalsis during rapid air distension. Whether current findings have therapeutic implication in the management of patients with globus sensation warrants further investigation.

[Effects of menopausal factor on fine anatomy of bladder urethra and vagina in women undergoing vaginal delivery].

Objective: To explore the effects of menopausal factor on fine anatomy of bladder, urethra and vagina in women undergoing vaginal delivery. Methods: Gynecological patients in Nanfang hospital from January 2013 to October 2016 were collected, and then the patients whose MRI images quality meet the require of reconstruction, with the history of vaginal delivery experience, without any cesarean section experience, and the first labor time was ≤30 years old were enrolled. The patients who had pelvic floor dysfunction when done MRI examinations were excluded. Finally, 238 cases were randomly selected out, and 238 models of data were reconstructed and measured by Mimics and UG software. The independent t test was used to do the comparison between menopausal group and those not yet menopause. Results: First, we built 238 3D models totally. Second, the parameters related with bladder and urethra: the angle of bladder and urethra, ß angle, urethra pubic angle, α angle, retropubic space, the length between bladder neck and edge of pubic midpoint, and urethral striated muscle thickness of menopausal group were bigger than those of pre-menopausal group. While for the urethra tilt angle, the former group was smaller than that of the latter group. But there was no significant statistical differences between two groups. Third, the parameters related with vagina: the proximal urethral vaginal gap of the post-menopause group was smaller than that of pre-menopausal group, while for the middle and distal urethral vaginal gap, the former group was bigger than that of the latter group. The length and width of vaginal anterior wall of the post-menopausal group were smaller than those of pre-menopausal group. Beside the middle urethral vaginal gap, all the difference between two groups had no statistical meaning. The 2D shape of axial vaginal, H type occupation of the former group was obviously lower than that of the latter group. Conclusions: Menopause has an effect on fine anatomy of pelvic organ. Especially on the shape of vagina, the middle urethral vaginal gap become much wider after menopause, the occupation of shallow concave type become much higher post-menopausal. It means the lateral and backward support function of the urethra and vagina is relatively weakened after menopausal, and the shape of vagina become smaller.

XUTs are a class of Xrn1-sensitive antisense regulatory non-coding RNA in yeast.

Non-coding (nc)RNAs are key players in numerous biological processes such as gene regulation, chromatin domain formation and genome stability. Large ncRNAs interact with histone modifiers and are involved in cancer development, X-chromosome inactivation and autosomal gene imprinting. However, despite recent evidence showing that pervasive transcription is more widespread than previously thought, only a few examples mediating gene regulation in eukaryotes have been described. In Saccharomyces cerevisiae, the bona-fide regulatory ncRNAs are destabilized by the Xrn1 5'-3' RNA exonuclease (also known as Kem1), but the genome-wide characterization of the entire regulatory ncRNA family remains elusive. Here, using strand-specific RNA sequencing (RNA-seq), we identify a novel class of 1,658 Xrn1-sensitive unstable transcripts (XUTs) in which 66% are antisense to open reading frames. These transcripts are polyadenylated and RNA polymerase II (RNAPII)-dependent. The majority of XUTs strongly accumulate in lithium-containing media, indicating that they might have a role in adaptive responses to changes in growth conditions. Notably, RNAPII chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) analysis of Xrn1-deficient strains revealed a significant decrease of RNAPII occupancy over 273 genes with antisense XUTs. These genes show an unusual bias for H3K4me3 marks and require the Set1 histone H3 lysine 4 methyl-transferase for silencing. Furthermore, abolishing H3K4me3 triggers the silencing of other genes with antisense XUTs, supporting a model in which H3K4me3 antagonizes antisense ncRNA repressive activity. Our results demonstrate that antisense ncRNA-mediated regulation is a general regulatory pathway for gene expression in S. cerevisiae.

Repeatability of vessel density measurement in human skin by OCT-based microangiography.

PURPOSE: To investigate the repeatability of vessel density measurement at human arm skin in healthy subjects with OCT-based microangiography (OMAG). METHODS: Four locations including volar wrist, volar forearm, shoulder, and volar upper arm were scanned using an optimized swept source OCT system, working at center wavelength of 1300 nm and A-line rate of 100 kHz. Three scans were acquired at each location at the same visit. Vascular images of papillary dermis, reticular dermis, and the whole dermis layer were generated with OMAG processing and automatic segmentation algorithms. The vessel density (VD) of each layer was calculated based on vascular images, and the repeatability of the VD at the same physiological location was thereafter assessed. RESULTS: Fifteen healthy volunteers were included. High repeatability of VD was found for wrist, forearm, shoulder, and upper arm (coefficient of variation (CV)=2.4, 2.7, 2.7, 2.0, and intraclass correlation coefficient (ICC)=0.906, 0.854, 0.943, 0.916 respectively). The VD measurements showed no significant difference between the four locations in any of the three layers, ie papillary layer (P=.1063), reticular layer (P=.3371), and whole dermis layer (P=.3233). CONCLUSION: Quantification of VD by using OCT/OMAG is repeatable when imaging skin tissue beds in healthy individuals.

Betulinic acid enhances TGF-ß signaling by altering TGF-ß receptors partitioning between lipid-raft/caveolae and non-caveolae membrane microdomains in mink lung epithelial cells.

BACKGROUND: TGF-ß is a key modulator in the regulation of cell proliferation and migration, and is also involved in the process of cancer development and progression. Previous studies have indicated that TGF-ß responsiveness is determined by TGF-ß receptor partitioning between lipid raft/caveolae-mediated and clathrin-mediated endocytosis. Lipid raft/caveolae-mediated endocytosis facilitates TGF-ß degradation and thus suppressing TGF-ß responsiveness. By contrast, clathrin-mediated endocytosis results in Smad2/3-dependent endosomal signaling, thereby promoting TGF-ß responsiveness. Because betulinic acid shares a similar chemical structure with cholesterol and has been reported to insert into the plasma membrane, we speculate that betulinic acid changes the fluidity of the plasma membrane and modulates the signaling pathway associated with membrane microdomains. We propose that betulinic acid modulates TGF-ß responsiveness by changing the partitioning of TGF-ß receptor between lipid-raft/caveolae and non-caveolae microdomain on plasma membrane. METHODS: We employed sucrose-density gradient ultracentrifugation and confocal microscopy to determine membrane localization of TGF-ß receptors and used a luciferase assay to examine the effects of betulinic acid in TGF-ß-stimulated promoter activation. In addition, we perform western blotting to test TGF-ß-induced Smad2 phosphorylation and fibronectin production. RESULTS AND CONCLUSIONS: Betulinic acid induces translocation of TGF-ß receptors from lipid raft/caveolae to non-caveolae microdomains without changing total level of TGF-ß receptors. The betulinic acid-induced TGF-ß receptors translocation is rapid and correlate with the TGF-ß-induced PAI-1 reporter gene activation and growth inhibition in Mv1Lu cells.